Elsa Johanna Louise Steen

Medicinal Chemistry Research

Current research

Bioorthogonal chemistry is an extension of the click chemistry and the term refers to chemical reactions that can occur without interfering with native biological processes. Two of the most highlighted bioorthogonal reactions are the Staudinger ligation and the strain-promoted azide-alkyne cycloaddition, which both have been widely used as labeling strategies for molecular imaging. However, these ligations are not optimal for in vivo imaging due to their slow reaction kinetics. A more useful ligation for this purpose is the inverse-electron-demand Diels-Alder (IEDDA) reaction between an electron deficient 1,2,4,5-tetrazine and a trans-cyclooctene (TCO), also known as the tetetrazine-trans-cyclooctene (TTCO) ligation. The TTCO ligation has fast reaction kinetics, stability towards functionalities in biological molecules and it can be conducted in water.

We aim to use the TTCO ligation as an approach for pretargeted in vivo imaging using positron emission tomography (PET). This pretargeted approach centers on target binding of a TCO-functionalized nanomedicine, followed by the administration of a radio-labeled tetrazine. The radio-labeled tetrazine will react with the TCO moiety, which allows imaging of the actual nanomedicine.